In order for a cell or organism to function effectively over the long term, genetic information must be stored stably in DNA. However, DNA undergoes constant modification as a result of random thermal collisions, including dupurination, and deamination of cytosine to uracil. DNA can also be modified by reactive molecules formed by metabolism of environmental agents and toxins, and by radiation and ultraviolet light. Yet only a very small fraction of changes in DNA cause a stable mutation. The rest are restored by DNA repair. The mechanisms of repair depend on the type of damage, and cells have evolved an elaborate machinery to make these repairs. Thus, the many genes that encode DNA repair functions are critical to cell survival, and may well be major determinants of life expectancy and the aging process. The broad objectives of this proposal are to assess the capacity of two parental inbred strains of mice to repair DNA damage as a function of age, and to see whether the DNA repair function can be localized to a specific region on chromosome 4, suing three congenic strains of mice derived from the parental strains. DNA repair will be assessed globally. This project will also serve as a model for a more general approach to using congenic mouse strains to analyze the individual genetic components of the biological basis of aging and age-related diseases.